A Study of Topical Pirenzepine or Placebo in Oncology Patients With Chemotherapy Induced Peripheral Neuropathy

Inclusion Criteria:

1. Males and females, ages > 18 years and older.

2. Scheduled to undergo chemotherapy for an advanced or metastatic (stage 3 or 4) solidtumor with carboplatin and paclitaxel for 6 cycles of treatment. Treatment withimmunotherapy agents Avastin (bevacizumab) and/or Keytruda (pembrolizumab) ispermitted.

3. Ability to sign informed consent and understand the nature of a placebo-controlledtrial.

4. ECOG Performance Status (PS) of 0, 1, or 2.

5. Ability to complete patient reported outcome questionnaires by themselves.

6. Life expectancy ≥ 6 months

7. Females should be either not of childbearing potential as a result of surgery ormenopause (1 year after onset), or of childbearing potential and must be practicinga highly effective medically acceptable method of contraception (as defined insection 8.4.4.1), including abstinence; hormonal contraceptives (e.g., combined oralcontraceptives, patch, vaginal ring, injectables, and implants); intrauterine deviceor intrauterine system; or vasectomy (partner), for at least 1 month before thescreening visit and for 1 month after the last dose of study medication. If accessor use of a highly effective medically acceptable method of contraception is notachievable, then a combination of barrier methods (e.g., male condom, female condom,cervical cap, diaphragm, contraceptive sponge) is acceptable. Eligible femalesubjects must also have a negative pregnancy test at the screening and baselinevisit.

8. Males must agree to the use an acceptable form of contraception (as defined insection 8.4.4.1) during sexual contact with a pregnant female or a female ofchildbearing potential while participating in the study (e.g., male condom withdiaphragm, male condom with cervical cap, or male condom in association withspermicide).

9. If diabetic, be on stable antidiabetic treatment (> 2 months prior to screening) (oral or injectable antidiabetic therapy and/or lifestyle) that is not anticipatedto change during the course of the study, except if medically required.

10. Fluency (oral and written) in the language in which the standardized tests will beadministered

Exclusion Criteria:

1. Pre-existing history (with or without current symptoms) in medical history of anytype of peripheral neuropathy due to any cause other than prior chemotherapy (diabetes, alcohol, toxins, neurotoxic treatments, hereditary, autoimmune, etc.).

2. Anyone with prior history of severe paclitaxel hypersensitivity (includinganaphylaxis) should be excluded from study enrollment. Pre-treatment is per localstandard of care guidelines to prevent a paclitaxel hypersensitivity reaction.Absolute Neutrophil Count (ANC) must be at least 1500 cells/mm3 prior to paclitaxeltreatment.

3. Currently taking regular pain medications i.e., gabapentin, pregabalin,amitriptyline or duloxetine. (Exception: opioids, given for the short-term treatmenti.e., malignant pain is acceptable. Opioids prescribed for neuropathic pain isexcluded).

4. Clinically significant active macrovascular disease, including a) myocardialinfarction or cerebrovascular event in the prior 6 months, b) angioplasty orstenting of coronary arteries or coronary artery bypass surgery within the past < 12months (valve replacements are permitted as long as patient has fully recovered fromthe surgery), c) diagnosis of congestive heart failure of any NY heart class I-IV,d) stable or progressive angina pectoris.

5. Other medical conditions, which in the opinion of the treating physician/alliedhealth professional would make this protocol unreasonably hazardous for the patient.

6. Vitamin E supplementation (2R-α-tocopherol or equivalent) for any reason > 225 IU (approximately 150mg)/day ≤ 30 days prior to randomization.

7. Any of the following: pregnant women, nursing women and men or women of childbearingpotential who are unwilling to employ adequate contraception (as defined in section 8.4.4.1).

8. Head or neck cancers.

9. Scheduled to undergo radiation therapy while on study.

10. History of hemorrhagic stroke.

11. Proliferative retinopathy or maculopathy requiring acute treatment.

12. Patients requiring dialysis.

13. Presence of clinically significant peripheral or autonomic neuropathy.

14. Current use local (topical) anesthetics or analgesics including lidocaine,capsaicin, cannabinoid (CBD) oil/products, or compounded topical pharmaceuticalagents.

15. Uncontrolled treated/untreated hypertension (systolic blood pressure [BP] ≥ 180 ordiastolic BP ≥ 100 at screening).

16. Amputations of lower extremities or presence of foot ulcers.

17. Uncontrolled or untreated hypothyroidism.

18. Active and/or systemic infections (e.g., HIV, hepatitis C, tuberculosis, syphilis),or a history of severe infection during the 30 days prior to screening.

19. Clinically significant gastric emptying abnormality (e.g., severe gastroparesis).

20. Clinically significant urinary retention or an enlarged prostate.

21. Uncontrolled glaucoma.

22. Other clinically significant, active or progressive (over the past 12 months)disease of the cardiovascular, gastrointestinal, pulmonary, renal, dermatologic,neurologic, genitourinary, endocrine, rheumatologic or hematologic systems that, inthe opinion of the Investigator, would compromise the subject's participation in thestudy, might confound the results of the study, or pose additional risk inadministering the study drug.

23. New treatment with (< 3 months) vitamins and supplements at the discretion of thePI.

24. Known or suspected history of alcohol or substance abuse (a stable and regular useof medical marijuana for non-neuropathic indications is acceptable).

25. Mental incapacity, unwillingness, or language barrier precluding adequateunderstanding of or cooperation with the study.

26. Women of childbearing potential must have a negative pregnancy test at screening andbaseline and must agree to use adequate contraceptive methods (as defined in section 8.4.4.1) during the study and for 1 month after the last dose of study drug (seeinclusion criterion 7).

27. History of allergy or hypersensitivity to anticholinergics or any of the componentsof the investigational product formulations (pirenzepine, coconut oil, ethanol,dimethyl sulfoxide (DMSO), surfactants, propylene glycol, etc.).

28. History of sensitive skin, as defined by a requirement to use soap and skin productsformulated for "sensitive skin," as determined by the Investigator.

29. Currently taking any medicines to treat overactive bladder (anticholinergic agents,such as Gelnique), or antispasmodics.

30. Inability to perform screening or baseline assessments. Patients with any condition that could potentially interfere with the conduct of thestudy or confound efficacy evaluations, including the following as specified innumbers 31 through 38 below:

31. Presence of pain, or any masquerading symptoms presenting as neuropathy includingcentral pain, radiculopathy, painful arthritis, etc., that could interfere with theinterpretation of the neuropathy endpoint assessments at the discretion of the PI.

32. Major skin or soft-tissue lesions in the dosing from below the knees to the bottomof both feet, and hands), small lesions (i.e., size of coin) are acceptable.However, topical application of study drug to these areas should be avoided.

33. Exposure to an experimental drug, experimental biologic, or experimental medicaldevice within 3 months before screening.

34. Any open wound(s) and/or sunburn(s) in the dosing area. Subjects who have a woundand/or sunburn at screening that is anticipated to resolve before day -1 can beenrolled.

35. History of a serious skin disease (as determined by the Investigator), such as skincancer, psoriasis, stasis dermatitis or eczema.

36. Receipt of a tattoo in the dosing area within 12 months of dosing.

37. Known or untreated Lyme disease.

38. Any abnormal or clinically significant lab or test result, collected from theScreening or Baseline visits that in the Investigator's opinion would not make thesubject an ideal participant in this trial.